Monoclonal antibodies have been used in earlier studies in this laboratory to identify and characterize the transferrin receptors of human and murine cells. Transferrin receptors are associated with active cell growth and are selectively expressed on some tumors in vivo. Monoclonal antibodies have been obtained that block receptor function and inhibit tumor cell growth in vitro. We will develop this work in two directions. In approaching our long-term objective of understanding the genetic regulation of transferrin receptors and of obtaining data that will contribute to a knowledge of the structure of the receptor, we will investigate methods to isolate the transferrin receptor gene of human cells, and we will derive cell mutants that have defects either in the expression or structure of the transferrin receptor. To obtain such mutants, selections will be carried out with antireceptor antibodies that directly block cell growth and with cytotoxic antibody-ricin A conjugates. We will also investigate the effects of monoclonal antibodies that inhibit transferrin receptor function in vitro on the growth of tumor cells in vivo in a mouse model system.